Vibegron shows potential as OAB treatment
The selective β3-adrenoreceptor (AR) agonist vibegron showed superior efficacy over placebo for overactive bladder (OAB) treatment and was generally well-tolerated, according to a Japanese study presented at EAU 2018.
“This is the first phase 3 study to demonstrate that vibegron is clinically useful and safe for the treatment of patients with OAB,” said the researchers.
A total of 1,232 patients with OAB symptoms for ≥6 months were randomized to receive vibegron 50 or 100 mg once daily (n=372 in each group), placebo (n=371), or the anticholinergic imidafenacin 0.2 mg twice daily as an active reference (n=117) for 12 weeks. [Eur Urol 2018;73:783-790; EAU 2018, abstract 1082]
At 12 weeks, vibegron 50 and 100 mg significantly reduced the mean number of micturitions/day compared with placebo (least squares [LS] mean, -2.08 and -2.03, respectively, vs -1.21; p<0.001 for both).
Both vibegron 50 and 100 mg showed superiority over placebo in resolving episodes of urgency (LS mean, -2.28; p<0.001 and LS mean, -2.44 vs -1.77; p<0.001 for 50 and 100 mg, respectively), urgency incontinence (LS mean, -1.35; p=0.001 and LS mean, -1.47 vs -1.08; p<0.001, respectively), incontinence (LS mean, -1.40; p=0.001 and LS mean, -1.53 vs -1.10; p<0.001, respectively), nocturia (LS mean, -0.58; p=0.016 and LS mean, -0.62 vs -0.47; p=0.001, respectively), and voided volume/micturition (LS mean, 33.55 mL; p<0.001 and LS mean, 29.96 vs 7.80 mL; p<0.001, respectively).
These findings reveal the sustained efficacy of vibegron, providing substantial control of micturition and resolution of symptoms throughout the study, they added.
Quality-of-life (QoL) evaluation revealed significant reductions in King’s Health Questionnaire scores for domains 1–9 ([D1–9] ie, general health perception, incontinence impact, role limitations, physical limitations, social limitations, personal relationships, emotions, sleep/energy, and severity measures) with vibegron 50 and 100 mg vs placebo (p<0.001 for both for D2–5 and D9; p=0.001 and p=0.011, respectively, for D7; and p=0.013 and p=0.010, respectively, for D8). The changes were nonsignificant for D1 and D6.
Patient Global Impression assessment revealed high satisfaction rates with vibegron 50 and 100 mg (90.8 percent and 91.6 percent, respectively), with 59.5 percent and 62.0 percent, respectively, claiming to be ‘very much satisfied’.
“[Evaluating] satisfaction levels [is important as] patient satisfaction is [believed] to be more sensitive than QoL in chronic diseases such as OAB,” said the researchers.
Treatment-emergent adverse events between vibegron 50 and 100 mg and placebo recipients were comparable (7.6 percent and 5.4 percent vs 5.1 percent), with the most common being constipation and dry mouth.
While these findings provide insight on vibegron as an alternative to oral anticholinergics which have been associated with limited efficacy and undesirable AEs, [Lancet Neurol 2004;3:46-53; Clin Ther 2013;35:1744-1751; Curr Opin Obstet Gynecol 2015;27:366-372] given the long-term treatment required for OAB, a treatment period beyond 12 weeks may be necessary to establish the real-world effects of vibegron, said the researchers. [Int J Clin Pract 2011;65:567-85]
“[Nonetheless,] vibegron improved not only QoL, but also patient satisfaction and objective improvements in the efficacy endpoints of the clinical study, suggesting that the drug is a favourable pharmacological management option for OAB,” said the researchers.
According to the researchers, the results align with studies reporting improved OAB symptoms with mirabegron, the first approved β3-AR agonist for OAB treatment. [Eur Urol 2017;72:389-399; J Med Econ 2017;20:614-622; BJU Int 2014;113:951-960] They recommended a head-to-head trial to compare their safety and efficacy and determine the risk of drug interactions. [Consult Pharm 2014;29:823-837]